Further definition of the MHC linkage relationships and detailed mapping of this region will be accomplished in the coming year. Specifically, the plan is to 1) procurement of antibodies against HLA-A,B,C, and DRw antigens and of homozygous typing cells. 2) type of families with or without HLA recombinants. 3) study the linkage of Br, C2 and C4 polymorphism to HLA. 4) study the relationship between HLA-Dw and DRw. 5) study the genetics of C2 and C4 deficiency in relation to HLA. We will also complete the first phase of assignment of C2 and Bf gene with hybrid cells. In future studies we also plan to address the following questions: (1) By what pathway could the formation in C3 of an internal thiolester proceed?; (2) What is the nature of the mechanism by which the thiolester is internally hydrolyzed and the acyl group transferred to components present on receptive surfaces?; and (3) could specific inhibitors of such a mechanism be found and the peptide containing the intact theolester isolated? Continuing with biosynthetic studies, we will further define the early synthetic events and post synthetic conversion of C4. C5 deficiency in humans will be studied in peripheral blood monocytes in order to define the biochemical basis of this condition.